SynthesisPsychological medicine2025
Disentangling the biological mechanisms underlying the effects of physical exercise in major depressive disorder: a comprehensive systematic review of randomized controlled trials.
Synthesis in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Causal inference in psychiatric research: how to critically evaluate and interpret mendelian randomization studies.Molecular psychiatry · 2026Review
- BDNF and IL-33 Dynamics in an Ultrasound Stress Model of Fibromyalgia-like Phenotypes.International journal of molecular sciences · 2026Article
- Correlation of physical activity with positive and negative affect and frontal lateralization in college students with depressive symptoms.Scientific reports · 2026Article
- The impact of physical exercise on depression among college students: the mediating role of core self-evaluation and meaning in life.Frontiers in psychology · 2026Article
- Occupational stress, cardiovascular vulnerability and sudden cardiac death in police officers: mechanisms and the protective role of structured exercise.Frontiers in public health · 2026Review
- Correlation analysis between sleep quality and depressive symptoms among rural elderly in China: An observational study.World journal of psychiatry · 2025Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMajor depressive disorder (MDD) is a disabling psychiatric condition in which physical activity provides clinical benefits. While exercise effectively alleviates depressive symptoms, its biological mechanisms remain unclear.
methodsThis systematic review investigated the neurobiological effects of physical exercise on biomarkers in adults with MDD through randomized controlled trials, including studies assessing exercise interventions and reporting data on their biological effects.
resultsA total of 30 studies, including 2194 participants, were included, examining the effects of physical exercise on various biological systems in patients with MDD. Exercise interventions had mixed effects on inflammatory markers, including interleukins, C-reactive protein, and tumor necrosis factor-α, suggesting a potential but inconsistent anti-inflammatory role. Neurotrophic factors, such as brain-derived neurotrophic factor showed promise as biomarkers of treatment response, but their role in clinical improvements remained inconclusive. Findings for the stress-response system, including cortisol and monoaminergic systems, primarily involving serotonin and dopamine, were limited and variable. Exercise demonstrated potential benefits in reducing oxidative stress and enhancing β-endorphin levels, although these effects were not consistently observed.
conclusionThis systematic review adopted a broader perspective than prior studies, exploring less-studied biological systems and identifying several limitations in the included studies, including small sample sizes, varying methodologies, and a predominant focus on biochemical markers. Future research should prioritize larger, standardized trials and particularly employ omics approaches to better understand the biological mechanisms underlying the effects of exercise in MDD. The findings highlight the complexity of exercise's biological effects and emphasize the need for further research to clarify its mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.